Tiny Human Stomachs Grown in Lab

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They may be small, but new lab-grown miniature human stomachs
could one day help researchers better understand how the stomach
develops, as well as the diseases that can strike it.

Using human stem cells and a series of chemical switches,
researchers grew stomachs measuring 0.1 inches (3 millimeters) in
diameter, in lab dishes, according to a report published today
(Oct. 29) in the journal Nature.

"It was really remarkable to us how much it looked like a
stomach," said researcher Jim Wells, a professor of developmental
biology at Cincinnati Children’s Hospital Medical Center.
[ See
images of the tiny stomachs ]

Growing a miniature stomach had its hurdles. There isn't much
information on how the human stomach forms during embryonic
development, so the researchers had to rely on basic research as
well as trial and error, Wells said. Also, the ability to grow
any three-dimensional organ in a lab is a fairly recent
development. Other researchers have grown flat samples of gastric
tissue, but few had successfully leapt into 3D territory, he
said.

The experiment began with
human pluripotent stem cells, which can become any cell in
the human body if given the right chemical instructions. The
researchers used two kinds of stem cells — one group was derived
from a human embryo that was made about 15 years ago, and the
other was derived from adult human skin cells, using a technique
that
won the Nobel Prize for medicine in 2012.

The researchers used chemicals to prompt the cells to create the
definitive endoderm, which is a flat layer of cells that forms
early during embryonic development. At this point, the cells
could still become other cells, including those forming the
liver, pancreas, lung or stomach.

Then, the researchers added two more proteins signals, to tell
the cells to form a three-dimensional tubelike structure called
the foregut.

"That's where we introduce our special mojo to go from 2D to 3D,"
Wells said. "We're triggering what would normally happen during
embryonic development, when embryos start kind of flat, and then
roll up into a three-dimensional embryo."

Other scientists working on regenerative medicine called the
development a big advance in gastric research.

"It's a beautiful study and very innovative," said Dr. Jason
Mills, an associate professor of gastroenterology at Washington
University School of Medicine in St. Louis, who was not involved
in the research. "We're now able to take individual human
patient's skin cells and turn them into little mini stomachs, or
really one portion of the stomach."

The organoids are not quite complete stomachs. The stomach is
divided into two parts, including one that makes the acid that
digests food, and another, the gastric antrum, that makes
proteins that control the production of acid and digestive
enzymes. The organiods include only the gastric antrum.

"We didn't make the part of the stomach that actually makes the
acid," but the researchers are now working on this, Wells said.

But the organoids can still help researchers learn about stomach
disease and development, said Dr. Tracy Grikscheit, an assistant
professor in pediatric surgery at the Keck School of Medicine at
the University of Southern California, who was not involved in
the study.

"In this paper, they effectively reproduce most of the components
of a portion of the stomach, the gastric antrum, allowing human
disease to be modeled in a dish instead of a patient," Grikscheit
told Live Science in an email. This may allow other scientists
"to make progress toward future human therapies," she said.

One application for the research will be using the stomachs to
study the effects of a bacterium called Helicobacter pylori, which causes gastric disease in
about 10 percent of people worldwide, and has been linked with
stomach conditions from ulcers to gastric cancer.

Research in animals hasn't turned out to be a good way to study
H. pylori's effects in people. The bacteria "doesn’t do
the same bad things when you put it into a mouse stomach," Wells
said.

Wells and his colleagues took the human stomach organoids to Yana
Zavros, an assistant professor of molecular and cellular
physiology at the University of Cincinnati, whose team injected
them with H. pylori.

"The bacteria did pretty much what we expected it to do," Wells
said, suggesting that the organoids are a good model for human
disease.

The organoids may also one day serve as a source of patches of
tissue that doctors could implant into patients with
ulcer-damaged stomachs, he added.